scholarly journals The pronounced decline of anti-SARS-CoV-2 spike trimeric IgG and RBD IgG in baseline seronegative individuals 6 months after BNT162b2 vaccination is consistent with the need for vaccine boosters

2021 ◽  
Author(s):  
Gian Luca Salvagno ◽  
Brandon M. Henry ◽  
Laura Pighi ◽  
Simone De Nitto ◽  
Gianluca Gianfilippi ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Severe Acute Respiratory Syndrome ◽  
Observational Study ◽  
Vaccine Dose ◽  
Serum Levels ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
Kinetics Of ◽  
Timely Administration ◽  
Median Rate

Abstract Background: This observational retrospective study aimed to define the kinetics of serum levels of anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) spike trimeric and anti-receptor binding domain (RBD) IgG antibodies up to 6 months after BNT162b2 vaccination. Methods: The sample consisted of 86 SARS-CoV-2 baseline seronegative subjects (median age 45 years, IQR 31-53 years; 52.3% females) undergoing vaccination with Pfizer/BioNTech BNT162b2. Blood was drawn before receiving the first and the second vaccine dose, as well as 1, 3 and 6 months after the second vaccine dose. The serum levels of anti-SARS-CoV-2 spike trimeric IgG and RBD IgG antibodies were assayed.Results: The peak of both antibodies types was reached 1 month after the second dose (2808 and 2163 BAU/mL for anti-SARS-CoV-2 spike trimeric IgG and RBD IgG), after which serum levels progressively declined, falling after 6 months to 486 BAU/mL and 167 BAU/mL for anti-SARS-CoV-2 spike trimeric IgG and RBD IgG, respectively. The median rate of 6-month decline was 85% and 93% for anti-SARS-CoV-2 spike trimeric IgG and RBD IgG, respectively. The rate of vaccine recipients with serum antibodies levels above the 80% threshold of vaccine efficacy declined from over 95% at the peak to 72% and 5% at 6 months for anti-SARS-CoV-2 spike trimeric IgG and RBD IgG, respectively.Conclusions: The results of this retrospective observational study are consistent with the need for timely administration of vaccine boosters to prevent that humoral immunity will wane.

scholarly journals Human IgG and IgA responses to COVID-19 mRNA vaccines

2021 ◽  
Author(s):  
Julian Campillo Luna ◽  
Adam V Wisnewski ◽  
Carrie A Redlich
Keyword(s):  
Vaccine Dose ◽  
Serum Levels ◽  
Rapid Decline ◽  
Natural Immunity ◽  
Limited Information ◽  
Viral Neutralization ◽  
Time To Peak ◽  
Specific Igg ◽  
Kinetics Of

SARS-CoV-2 spike antigen-specific IgG and IgA elicited by infection mediate viral neutralization and are likely an important component of natural immunity, however, limited information exists on vaccine induced responses. We measured COVID-19 mRNA vaccine induced IgG and IgA in serum serially, up to 80 days post vaccination in 4 subjects. Spike antigen-specific IgG levels rose exponentially and plateaued 21 days after the initial vaccine dose. After the second vaccine dose IgG levels increased further, reaching a maximum approximately 7-10 days later, and remained elevated (average of 78% peak levels) during the additional 20-50 day follow up period. COVID-19 mRNA vaccination elicited spike antigen-specific IgA with similar kinetics of induction and time to peak levels, but more rapid decline in serum levels following both the 1st and 2nd vaccine doses (<23% peak levels within 80 days of the initial shot). The data demonstrate COVID-19 mRNA vaccines effectively induce spike antigen specific IgG and IgA and highlight marked differences in their persistence in serum.

scholarly journals Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in patients with COVID-19

2020 ◽  
Vol 5 (52) ◽  
pp. eabe5511
Author(s):  
Baweleta Isho ◽  
Kento T. Abe ◽  
Michelle Zuo ◽  
Alainna J. Jamal ◽  
Bhavisha Rathod ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Receptor Binding ◽  
Antibody Responses ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
Surrogate Measure ◽  
Antibody Levels ◽  
Negative Controls

Although the antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been extensively studied in blood, relatively little is known about the antibody response in saliva and its relationship to systemic antibody levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) immunoglobulin G (IgG), IgA, and IgM responses to the SARS-CoV-2 spike protein (full-length trimer) and its receptor binding domain (RBD) in serum and saliva of acute and convalescent patients with laboratory-diagnosed coronavirus disease 2019 (COVID-19) ranging from 3 to 115 days postsymptom onset (PSO), compared with negative controls. Anti–SARS-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16 to 30 days PSO. Longitudinal analysis revealed that anti–SARS-CoV-2 IgA and IgM antibodies rapidly decayed, whereas IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. Last, IgG, IgM, and, to a lesser extent, IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that serum and saliva IgG antibodies to SARS-CoV-2 are maintained in most of the patients with COVID-19 for at least 3 months PSO. IgG responses in saliva may serve as a surrogate measure of systemic immunity to SARS-CoV-2 based on their correlation with serum IgG responses.

scholarly journals Evaluation of Anti-SARS-Cov-2 S-RBD Igg Antibodies after COVID-19 mRNA BNT162b2 Vaccine

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1135
Author(s):  
Bruna Lo Sasso ◽  
Rosaria Vincenza Giglio ◽  
Matteo Vidali ◽  
Concetta Scazzone ◽  
Giulia Bivona ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
Chemiluminescence Immunoassay ◽  
Protein Receptor ◽  
Short Period ◽  
Previous Infection ◽  
Individual Protection ◽  
The Individual

(1) Background: The evaluation of anti-spike protein receptor-binding domain (S-RBD) antibodies represents a useful tool to estimate the individual protection against Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection; (2) Methods: We evaluated anti S-RBD IgG levels by indirect chemiluminescence immunoassay on Maglumi 800 (SNIBE, California) in 2248 vaccinated subjects without previous SARS-CoV-2 infection, 91 vaccinated individuals recovered from COVID-19, and 268 individuals recovered from COVID-19 who had not been vaccinated. Among those who were healthy and vaccinated, 352 subjects performed a re-dosing after about 72 days from the first measurement. (3) Results: Anti S-RBD IgG levels were lower in subjects with previous infection than vaccinated subjects, with or without previous infection (p < 0.001). No difference was observed between vaccinated subjects, with and without previous SARS-CoV-2 infection. Overall, anti-RBD IgG levels were higher in females than males (2110 vs. 1341 BAU/mL; p < 0.001) as well as in subjects with symptoms after vaccination than asymptomatic ones (2085 vs. 1332 BAU/mL; p = 0.001) and lower in older than younger subjects. Finally, a significant decrease in anti-RBD IgG levels was observed within a short period from a complete two-dose cycle vaccination. (4) Conclusions: Our results show an efficacy antibody response after vaccination with age-, time- and sex-related differences.

scholarly journals Human IgG and IgA responses to COVID-19 mRNA vaccines

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0249499
Author(s):  
Adam V. Wisnewski ◽  
Julian Campillo Luna ◽  
Carrie A. Redlich
Keyword(s):  
Vaccine Dose ◽  
Serum Levels ◽  
Rapid Decline ◽  
Natural Immunity ◽  
Limited Information ◽  
Viral Neutralization ◽  
Time To Peak ◽  
Specific Igg ◽  
Kinetics Of

SARS-CoV-2 spike antigen-specific IgG and IgA elicited by infection mediate viral neutralization and are likely an important component of natural immunity, however, limited information exists on vaccine induced responses. We measured COVID-19 mRNA vaccine induced IgG and IgA in serum serially, up to 145 days post vaccination in 4 subjects. Spike antigen-specific IgG levels rose exponentially and plateaued 21 days after the initial vaccine dose. After the second vaccine dose IgG levels increased further, reaching a maximum approximately 7–10 days later, and remained elevated (average of 58% peak levels) during the additional >100 day follow up period. COVID-19 mRNA vaccination elicited spike antigen-specific IgA with similar kinetics of induction and time to peak levels, but more rapid decline in serum levels following both the 1st and 2nd vaccine doses (<18% peak levels within 100 days of the 2nd shot). The data demonstrate COVID-19 mRNA vaccines effectively induce spike antigen specific IgG and IgA and highlight marked differences in their persistence in serum.

scholarly journals Six-month decline of serum anti-spike S1 subunit IgA in SARS-CoV-2 in seronegative healthcare workers after mRNA-based COVID-19 vaccination

2021 ◽  
Author(s):  
Gian Luca Salvagno ◽  
Brandon M. Henry ◽  
Laura Pighi ◽  
Simone De Nitto ◽  
Giuseppe Lippi
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Observational Study ◽  
Peak Concentration ◽  
Healthcare Workers ◽  
Vaccine Dose ◽  
Inverse Correlation ◽  
Virus Neutralization ◽  
Serum Samples ◽  
Significant Inverse Correlation ◽  
Iga Antibodies

Abstract Background: Since serum anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) IgA antibodies correlate with secretory anti-SARS-CoV-2 IgA and contribute to virus neutralization, we planned an observational study to measure serum anti-SARS-CoV-2 IgAs kinetics throughout a 6-month period in coronavirus disease 2019 (COVID-19) vaccine recipients.Methods: The study sample consisted of 97 baseline SARS-CoV-2 seronegative healthcare workers (median age 42 years and IQR 31-52 years; 52 females), who underwent vaccination with Pfizer/BioNTech Comirnaty mRNA-based vaccine (two 30 µg doses, 21 days apart). Serum samples were collected at baseline, before the second vaccine dose (i.e., day 21), and then 51, 111 and 201 days after enrolment (i.e., 1, 3 and 6 months after the second vaccine dose). Serum anti-SARS-CoV-2 spike S1 subunit IgA were measured with Anti-SARS-CoV-2 ELISA IgA (Euroimmun, Lübeck, Germany).Results: Anti-SARS-CoV-2 spike S1 subunit IgA displayed a peak at 1 month after the second vaccine dose, but then progressively waned afterwards. The 6-month serum anti-spike S1 subunit IgA concentration was 71% lower than the peak concentration. The rate of subjects with positive IgA values was 0% at baseline, 80.4% at day 21, 97.9% at day 51, but then declined to 73.2% and 53.6% at 3 and 6 months after the second vaccine dose. Serum anti-spike S1 subunit IgAs measured at 111 and 201 days was significantly lower than at the 51-day peak (both p<0.001). Significant inverse correlation was found between anti-SARS-CoV-2 IgA antibodies decline at 6 months/ and recipients’ age (r=-0.24; p=0.019).Conclusion: These findings may provide possible explanation to decreased efficacy of COVID-19 vaccines in preventing SARS-CoV-2 infection 6 months after vaccination.

scholarly journals Prospective Cohort Study of the Kinetics of Specific Antibodies to SARS-CoV-2 Infection and to Four SARS-CoV-2 Vaccines Available in Serbia, and Vaccine Effectiveness: A 3-Month Interim Report

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1031
Author(s):  
Olivera Lijeskić ◽  
Ivana Klun ◽  
Marija Stamenov Djaković ◽  
Nenad Gligorić ◽  
Tijana Štajner ◽  
...  
Keyword(s):  
Real Life ◽  
Vaccine Dose ◽  
Igg Antibodies ◽  
Post Vaccination ◽  
Specific Antibodies ◽  
Real Life Data ◽  
Specific Igg ◽  
Antibody Levels ◽  
Kinetics Of ◽  
Specific Igg Antibodies

Real-life data on the performance of vaccines against SARS-CoV-2 are still limited. We here present the rates of detection and levels of antibodies specific for the SARS-CoV-2 spike protein RBD (receptor binding domain) elicited by four vaccines available in Serbia, including BNT-162b2 (BioNTech/Pfizer), BBIBP-CorV (Sinopharm), Gam-COVID-Vac (Gamaleya Research Institute) and ChAdOx1-S (AstraZeneca), compared with those after documented COVID-19, at 6 weeks and 3 months post first vaccine dose or post-infection. Six weeks post first vaccine dose, specific IgG antibodies were detected in 100% of individuals fully vaccinated with BNT-162b2 (n = 100) and Gam-COVID-Vac (n = 12) and in 81.7% of BBIBP-CorV recipients (n = 148), while one dose of ChAdOx1-S (n = 24) induced specific antibodies in 75%. Antibody levels elicited by BNT-162b2 were higher, while those elicited by BBIBP-CorV were lower, than after SARS-CoV-2 infection. By 3 months post-vaccination, antibody levels decreased but remained ≥20-fold above the cut-off in BNT-162b2 but not in BBIBP-CorV recipients, when an additional 30% were seronegative. For all vaccines, antibody levels were higher in individuals with past COVID-19 than in naïve individuals. A total of twelve new infections occurred within the first 3 months post-vaccination, eight after the first dose of BNT-162b2 and ChAdOx1-S (one each) and BBIBP-CorV (six), and four after full vaccination with BBIBP-CorV, but none required hospitalization.

scholarly journals Total anti-SARS-CoV-2 antibodies measured 6 months after Pfizer-BioNTech COVID-19 vaccination in healthcare workers

2021 ◽  
Author(s):  
Giuseppe Lippi ◽  
Gian Luca Salvagno ◽  
Brandon Michael Henry ◽  
Laura Pighi ◽  
Simone De Nitto
Keyword(s):  
Healthcare Workers ◽  
Venous Blood ◽  
Vaccine Dose ◽  
Serum Levels ◽  
Gradual Decline ◽  
Post Vaccination ◽  
Median Serum ◽  
Study Population ◽  
Kinetics Of

Background: This study aimed at monitoring the kinetics of serum total anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antibodies in a cohort of healthcare workers after voluntary vaccination with Pfizer-BioNTech coronavirus disease 2019 (COVID-19).Methods: The study population consisted of 787 healthcare workers (mean age 44±12 years; 66% females), who received two 30 μg doses of Pfizer-BioNTech COVID-19 vaccine, 3 weeks apart. Venous blood was drawn before the first vaccine dose, immediately before the second vaccine dose, and then at 1, 3 and 6 months after the second vaccine dose. Serological testing employed the total anti-SARS-CoV-2 antibodies measurement with Roche Elecsys Anti-SARS-CoV-2 S chemiluminescent immunoassay.Results: The median serum levels of total anti-SARS-CoV-2 antibodies reached the peak (1762 KU/L) 1 month after the second vaccine dose, but tended to progressively decline at the 3-month (1086 KU/L) and 6-month (802 KU/L) follow-up points. Overall, the values after 3- and 6-months were 37% and 57% lower than the corresponding concentrations measured at the peak. No healthcare worker had total anti-SARS-CoV-2 antibodies below the method-dependent cut-off. The decline compared to the peak was more accentuated in baseline seropositive persons than in those who were baseline seronegative (74% vs. 52%) cohort. The 6-month post-vaccination anti-SARS-CoV-2 antibodies in subjects aged <65 years remained over 2-fold higher than that measured in those aged ≥65 years (813 vs. 343 KU/L). Conclusions: Gradual decline of total anti-SARS-CoV-2 antibodies occurred 6 months after Pfizer-BioNTech COVID-19 vaccination, though values remained higher than the method-dependent cut-off, with no case of seronegativization.

scholarly journals Efficacy and safety of a third SARS-CoV-2 vaccination in multiple sclerosis vaccine non-responders

2021 ◽  
Author(s):  
Marton Konig ◽  
Hilde Marie Torgauten ◽  
Marthias Herstad Overas ◽  
Adity Chopra ◽  
Aslaug Rudjord Lorentzen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Side Effects ◽  
Severe Acute Respiratory Syndrome ◽  
Humoral Immunity ◽  
Vaccine Dose ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Efficacy And Safety ◽  
Immunization Registry ◽  
Anti Cd20

Importance: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to protect against coronavirus disease of 2019 (COVID-19) is recommended for patients with multiple sclerosis (pwMS). However, approximately 80% of all pwMS treated with anti-CD20 therapy (rituximab, ocrelizumab) or fingolimod have low or absent humoral immunity after vaccination with two doses of SARS-CoV-2 mRNA vaccines. The efficacy and safety of a third vaccine dose in this group is largely unknown. Objective: To characterize the humoral immunogenicity and the safety of a third dose of mRNA-COVID-19 vaccine in anti-CD20- or fingolimod-treated pwMS with low or absent humoral immunity (i.e., anti-SARS-CoV-2 IgG <70 arbitrary units (AU) and <5 AU, respectively) after two vaccinations. Design, setting and participants: 130 anti-CD20- or fingolimod-treated pwMS with low or absent humoral immunity despite full vaccination against SARS-CoV-2, received a third dose of SARS-CoV-2 mRNA vaccine. Humoral immunity (i.e., antibody response against SARS-CoV-2) and the frequency and characteristics of side-effects were analyzed in all participants. Exposures: A third vaccine dose against SARS-CoV-2 with BNT162b2- or mRNA-1273-COVID-19 vaccine. Main outcomes and measures: Patient- and treatment-specific variables were acquired using a digital questionnaire, the Norwegian Immunization Registry and hospital journals. Humoral immunity was assessed by measuring SARS-CoV-2 SPIKE receptor-binding domain (RBD) IgG response. Low/absent humoral immunity was assumed in cases of AU<70 after anti-SPIKE protein-based serology 3-5 weeks after revaccination. Results: A third dose of SARS-CoV-2 mRNA vaccine increased anti-SARS-CoV-2 SPIKE RBD IgG levels significantly. The proportion of patients with assumed protective humoral immunity (anti-SARS-CoV-2 SPIKE RBD IgG > 70 AU) were 25% among patients using anti-CD20 therapy and 7% among those treated with fingolimod. No adverse events were registered during the study period. Conclusion and relevance: A third dose of mRNA-COVID-19 vaccine was associated with significantly increased levels of anti-SARS-CoV-2 SPIKE RBD IgG, and hence assumed protective humoral immunity - in anti-CD20- or fingolimod-treated pwMS with low or absent humoral immunity despite full vaccination. The effect of a third vaccine dose was limited and more prominent among those treated with anti-CD20 therapy.

scholarly journals Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ariel Munitz ◽  
L. Edry-Botzer ◽  
M. Itan ◽  
R. Tur-Kaspa ◽  
D. Dicker ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Neutralizing Antibodies ◽  
Host Response ◽  
Humoral Response ◽  
Rapid Onset ◽  
Response Analysis ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
Viral Receptor ◽  
Iga Antibodies

AbstractDespite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.

scholarly journals Immunogenicity and Neutralizing Activity Comparison of SARS-CoV-2 Spike Full-Length and Subunit Domain Proteins in Young Adult and Old-Aged Mice

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 316
Author(s):  
Ki-Hye Kim ◽  
Noopur Bhatnagar ◽  
Subbiah Jeeva ◽  
Judy Oh ◽  
Bo Ryoung Park ◽  
...  
Keyword(s):  
Young Adult ◽  
Receptor Binding ◽  
Vaccine Dose ◽  
The Elderly ◽  
Full Length ◽  
High Dose ◽  
Igg Antibodies ◽  
Neutralizing Activity ◽  
Aged Mice ◽  
Adjuvant Effects

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be expanding the pandemic disease across the globe. Although SARS-CoV-2 vaccines were rapidly developed and approved for emergency use of vaccination in humans, supply and production difficulties are slowing down the global vaccination program. The efficacy of many different versions of vaccine candidates and adjuvant effects remain unknown, particularly in the elderly. In this study, we compared the immunogenic properties of SARS-CoV-2 full-length spike (S) ectodomain in young adult and aged mice, S1 with receptor binding domain, and S2 with fusion domain. Full-length S was more immunogenic and effective in inducing IgG antibodies after low dose vaccination, compared to the S1 subunit. Old-aged mice induced SARS-CoV-2 spike-specific IgG antibodies with neutralizing activity after high dose S vaccination. With an increased vaccine dose, S1 was highly effective in inducing neutralizing and receptor-binding inhibiting antibodies, although both S1 and S2 subunit domain vaccines were similarly immunogenic. Adjuvant effects were significant for effective induction of IgG1 and IgG2a isotypes, neutralizing and receptor-binding inhibiting antibodies, and antibody-secreting B cell and interferon-γ secreting T cell immune responses. Results of this study provide information in designing SARS-CoV-2 spike vaccine antigens and effective vaccination in the elderly.

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